Malaria is one of the most prevalent infections in tropical and subtropical areas throughout the world. Malaria infections lead to severe illnesses in hundreds of millions of individuals worldwide, leading to death in millions of individuals, primarily in developing and emerging countries every year. The widespread occurrence and elevated incidence of malaria are a consequence of the increasing numbers of drug-resistant parasites and insecticide-resistant parasite vectors. Other factors include environmental and climatic changes, civil disturbances, and increased mobility of populations.
Malaria is caused by the mosquito-borne hematoprotozoan parasites belonging to the genus Plasmodium. Four species of Plasmodium protozoa (P. falciparum, P. vivax, P. ovale and P. malariae) are responsible for the disease in man; many others cause disease in animals, such as P. yoelii and P. berghei in mice. P. falciparum accounts for the majority of human infections and is the most lethal type, sometimes called “tropical malaria”. Malaria parasites have a life cycle consisting of several stages. Each stage is able to induce specific immune responses directed against the corresponding occurring stage-specific antigens. A current area of focus is development of vaccines that elicit immunity against the sporozoite stage pathogen. The sporozoite grows in the saliva of infected mosquitoes and is transferred to the human during the mosquito bite. The sporozoite travels thorough the blood stream to the liver where it enters hepatocytes and multiplies. Sporozoites are covered with many copies of the circumsporozoite coat protein (CS). Antibodies that bind to CS proteins can neutralize the organism and prevent liver invasion, so agents that elicit potent and long lasting anti-CS responses are expected to be useful malaria vaccines.
Currently there are two vaccines in clinical trials that seek to prevent malaria infections via the CS neutralization mechanism. RTS,S is a virus like particle vaccine that presents multiple copies of CS on a virus-like particle. It has been shown to protect both adults and children from infection but since efficacy is less than 50% its utility is still a matter for debate. Sanaria Inc. has proposed the use of killed sporozoites as an effective vaccine but the method of production involves the dissection of host mosquito saliva glands, a process that is tedious and may not be scalable to practical quantities. Hence there is a need for improved antigenic compositions that elicit immune responses which recognize and neutralize the malaria organism.